Project Summary/Abstract The COVID-19 pandemic is a worldwide emergency causing major social and economic disruptions. As an emergent viral infection, there are major knowledge gaps regarding COVID-19. In particular, there is limited information thus far on the impact of COVID-19 on pregnant women and their infants. Initial studies suggest that clinical manifestations during pregnancy are similar to those identified in non-pregnant adults, and recent reports have described cases of severe pneumonia and ARDS in pregnant women. Information on the impact of maternal infection on the infant is also limited. Investigators in China documented perinatal transmission in a small number of newborn infants. A common feature of severe COVID-19 appears to be inflammation, which is a known risk factor for poor pregnancy outcomes and can impact the development of the infant immune system. Thus, there is an urgent need to understand the role of COVID-19 during pregnancy and its impact on the infant. Our Parent U01 is focused on high-resolution analysis of immune responses in healthy infants. The goal of this supplement is to determine how maternal COVID-19 infection affects the infant immune system, which we will achieve by analyzing the interplay between the maternal and infant immune systems in the context of COVID- 19. We hypothesize that COVID-19 during pregnancy leaves a stable imprint on the infant immune system defined by enhanced inflammation and dysregulated responses to vaccines. Although our focus is the analysis of infant immune responses, a comprehensive system analysis approach is required to efficiently identify the most relevant immunologic and virologic factors that determine COVID-19 outcomes in pregnant women, and how they impact the immune responses of the fetus and the infant. We propose conducting a prospective longitudinal study in pregnant women with COVID-19 occurring at any time during pregnancy and follow their infants longitudinally to assess their immune responses until 7 months of age. As a reference control, we will include a cohort of non-COVID-19 pregnant women and their infants.